DESCRIPTION (provided by investigator): Influenza vaccine is the most widely used control measure for influenza, but estimates of the effectiveness of vaccine against laboratory confirmed influenza are lacking in many high risk populations. In addition, the relationship between antigenic variation and vaccine effectiveness is incompletely understood in many populations. These gaps in our understanding hinder efforts to use influenza vaccines effectively, and have generated doubts among practitioners regarding the utility of vaccine in some populations, notably the elderly. The proposed studies will use a case control approach to assess the effectiveness of influenza vaccine in preventing laboratory-confirmed medically attended acute respiratory illness. Individuals seeking care as inpatients, in emergency departments, and in outpatient clinics will be tested for the presence of a variety of respiratory viruses, and vaccination histories in influenza positive cases will be compared with controls who are positive for respiratory syncytial virus, human metapneumovirus, or rhinovirus. Two broad populations will be assessed: children from 6 months of age to 13 years, and adults 50 years of age and older. Both logistic regression and Cox proportional hazard models will be utilized to determine effectiveness after adjusting for a number of covariates. A key feature of the analysis will be the detection of other respiratory viruses to identify controls, which avoids the problem of misclassification of cases due to possible inaccuracies in diagnostic testing. In addition, we will obtain peripheral blood from healthy young adults and elderly adults before and after influenza vaccination for assessment of humoral and cellular immune responses that may be related to the degree of protective efficacy seen. The application takes advantage of the existence of several strong, synergistic programs at the University of Rochester, including the New Vaccines Surveillance Network (NVSN), the Emerging Infections Program (EIP), and the New York Influenza Center of Excellence (NYICE). Successful completion of these studies will provide insight into the utility of influenza vaccine in various target groups, the relationship between antigenic variation and vaccine effect, and between immune responsiveness and effectiveness.